Plasmids of incompatibility group P (IncP) are remarkable for their autonomous replication in a wide variety of gram(-) bacteria and their conjugal transfer to gram(+) and gram(-) bacteria and yeast. They are valuable as tools for the genetic analysis of diverse bacteria of clinical, environmental, and technological importance. The promiscuity of IncP plasmids presents a significant health problem with respect to the dissemination and maintenance of antibiotic resistance genes among bacteria. Multiply resistant IncP plasmids have been isolated from a variety of bacterial species worldwide. The objective of these studies on the IncP plasmid RK2 is to understand the molecular and genetic basis for the replication and conjugal promiscuity of IncP plasmids. Studies by this laboratory revealed that RK2 displays a genetic complexity unmatched by any other group of plasmids. Eight operons are coregulated by various combinations of the negative-control determinants korA, B, C, E, F, and trbA. This regulatory network, the kil-kor regulon, encodes the replication initiator (trfA operon), transfer functions (kilB operon), regulatory genes (korABF operon), and unknown functions (kilA operon, kilC operon, kfrA operon, and two kilE operons). The host-lethal kil functions are proposed to be important for maintenance or host range. These studies will investigate mechanisms of RK2 gene regulation, functions of genes of the kil operons, and plasmid-host interactions. It is anticipated that these studies will increase the understanding of the basis for survival and dissemination of IncP plasmids in nature and provide new insights into plasmid-host relationships.